CD73 (NT5E) Promotes the Proliferation and Metastasis of Lung Adenocarcinoma through the EGFR/AKT/mTOR Pathway

Biomed Res Int. 2022 Jun 29:2022:9944847. doi: 10.1155/2022/9944847. eCollection 2022.

Abstract

Introduction: Lung cancer is the most common malignant tumor and the main cause of tumor-related death globally. As the 5-year survival rate of lung adenocarcinoma (LUAD) remains low, it is necessary to investigate novel molecular markers and therapeutic targets for LUAD.

Materials and methods: The protein expression of CD73 (NT5E) in LUAD specimens was analyzed using immunohistochemistry. Reverse transcription-quantitative PCR and western blot analysis were used to analyze the mRNA and protein expression levels of several genes in LUAD cells. The proliferation of LUAD cells was evaluated using proliferation and colony formation assays and apoptosis analysis. Wound healing and Transwell invasion assays were used to analyze the migration and invasion of the A549 cells, respectively. In addition, overexpression plasmids and small interfering RNAs were used to overexpress or knockdown the expression levels of CD73 in the A549 cell line, respectively. Finally, the interaction between CD73 and EGFR in the A549 cell line was analyzed using immunoprecipitation.

Results: Our research emphasized the importance of CD73 in the prognosis of LUAD and highlighted it as a potential therapeutic target. We also found that the mRNA and protein expression levels of CD73 are increased in LUAD specimens and cell lines and were associated with a poor prognosis in patients with LUAD. Furthermore, it was revealed that CD73 may promote the proliferation, migration, and invasion of the A549 cell line. Finally, we demonstrated that CD73 could bind epidermal growth factor receptor (EGFR) to further regulate the activation of the AKT/mTOR signaling pathway.

Conclusions: CD73 promotes LUAD proliferation and metastasis through EGFR/AKT/mTOR axis.

Publication types

  • Retracted Publication

MeSH terms

  • 5'-Nucleotidase / genetics
  • 5'-Nucleotidase / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • GPI-Linked Proteins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / pathology
  • Neoplastic Processes
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • GPI-Linked Proteins
  • RNA, Messenger
  • MTOR protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • 5'-Nucleotidase
  • NT5E protein, human